Pulmonary surfactant is produced by the fetus in significant amount towards the end of gestation. A number of hormones have been shown to accelerate fetal lung maturation and surfactant production. We will determine the mechanism by which estrogens, glucocorticoids and thyrotropin-releasing hormone (TRH) stimulate surfactant production in the fetal rabbit. We will determine the effect of maternal estrogen administration on the rate of incorporation of precursors into various phospholipids, protein and DNA in the fetal lung. We will determine its effect on the activities of enzymes of pulmonary phosphatidylcholine and phosphatidylglycerol biosynthesis. We will determine if estrogen administration increases the rate of survival of premature fetal rabbits, whether it accelerates morphological maturation of the fetal lung and if it has an effect on fetal lung glycogen biochemistry. We will determine if the fetal lung contains a specific estrogen receptor. We will determine if the effect of estrogen is organ and species specific. We will determine the mechanism by which betamethasone administration to pregnant rabbits increases the activity of fetal lung cholinephosphate cytidylyltransferase. We will determine if phosphatidylglycerol is involved in this process. We will also determine if there is a similar effect on ethanolaminephosphate cytidylyltransferase. We will determine if the effect of betamethasone on enzyme activities is due to synthesis of new protein. We will determine the mechanism by which TRH stimulates fetal lung maturation: whether it acts via the fetal thyroid hormone, via prolactin or by a direct effect on the lung. We will determine the effects of combinations of the above hormones on fetal lung maturation and we will use agonists and inhibitors in an effort to elucidate the hormonal control of surfactant production in the fetus. These studies should lead to a better understanding of the mechanism of surfactant production in the fetus. This is essential in order to develop rational therapeutic approaches to the prevention of the Respiratory Distress Syndrome of the Newborn(RDS) which is believed to be due to immaturity of the lung with insufficient pulmonary surfactant.